Pseudotargeted metabolomics for exploring the changes of neurotransmitters profile in aging rat brain and the potential neuroprotective effect of alkaloids from Uncaria rhynchophylla  

作　　者：Shi-Wei Li Yi-Song Wu Shi-Fei Wu Wen-Long Wei Ming-Yang Qiu Yun Li De-An Guo 

机构地区：[1]College of Pharmacy,Changchun University of Chinese Medicine,Changchun 130117,China [2]Shanghai Research Center for Modernization of Traditional Chinese Medicine,National Engineering Research Center of TCM Standardization Technology,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China

出　　处：《Traditional Medicine Research》2022年第5期1-9,共9页TMR传统医学研究

基　　金：supported by the Shanghai Sailing Program(No.21YF1455800);the National Key R&D Program of China(No.2019YFC1711000);the Qi-Huang Scholar of National Traditional Chinese Medicine Leading Talents Support Program(No.2018);the Chief Scientist of Qi-Huang Project of National Traditional Chinese Medicine Inheritance and Innovation“One Hundred Million”Talent Project(No.2020).

摘　　要：Background:Aging is an essential risk factor for most neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s disease.However,changes in the levels of neurotransmitters that are associated with aging are not well understood.Methods:Methods such as liquid-liquid extraction,protein precipitation,and solid-phase extraction,using 20 different extraction solvents,were evaluated to optimize the extraction of neurotransmitters.A pseudotargeted metabolomics approach was developed to detect neurotransmitters in brain tissues using ultra-high-performance liquid chromatography coupled with tandem triple quadrupole mass spectrometry.Alkaloids that crossed into the brain were used to evaluate the effect of glutamic acid-induced excitatory neurotoxicity in SH-SY5Y cells.Results:The overall extraction efficiency using protein precipitation was high.The changes in neurotransmitters’levels in the brain exhibited changes during the different growth cycles.The levels of seven neurotransmitters(aspartic acid,tyrosine,isoleucine,leucine,tryptophan,valine,andγ-aminobutyric acid)were significantly different.Meanwhile,alkaloids could reduce the excitatory neurotoxicity of glutamic acid-induced SH-SY5Y cells via suppression of oxidative stress.Conclusion:Significant differences were observed in neurotransmitter profiling between 1-and 8-month-old rats,and the discrepant neurotransmitters were associated with aging.Seven indole alkaloids from Uncaria rhynchophylla,which could cross the blood-brain barrier,were screened and used to explore their protective effects against aging.Uncaria rhynchophylla alkaloids exhibited a neuroprotective effect by inhibiting oxidative stress,indicating that the alkaloid could be a potential therapeutic candidate for neurological disorders caused by glutamic acid toxicity.

关 键 词：NEUROTRANSMITTERS AGING Uncaria rhynchophylla indole alkaloids neuroprotective effect pseudotargeted metabolomics 

分 类 号：O62[理学—有机化学]